Overexpression of the p73 gene is a novel finding in high-risk B-cell chronic lymphocytic leukemia

The p73 protein shares structural and functional similarities with the tumour-suppressor p53, but its role in neoplastic transformation is unknown. Alternative splicing leads to the expression of at least nine p73 C-terminal mRNA splice variants (α β γ δ ε ξ η ηl θ). In this survey, we analyse the expression of p73 by real-time quantitative RT-PCR, its known C-terminal variants with an RT-PCR-Southern tech nique and by Western blot in samples of 51 patients with B-CLL, normal B lymphocytes from eight individuals, and five haematopoetic cell lines. p73α protein expression positively correlated with higher risk B-CLL stages (P=0.046). Total p73 mRNA expression was higher (P= 0.01) and p73α protein more frequently detected (P=0.008) in B-CLL compared with normal CD19+—B-lymphocytes. p73 C-terminal mRNA variants were expressed both in B-CLL and in normal B-lymphocytes, but their expression was biased since the γ (P=0.041), the θ (P ≪ 0.001), and the η variant (P=0.033) prevailed in normal B-lymphocytes. In summary, we conclude that the accumulation of p73, the expression pattern of particular p73 variants and its link to progression may play a distinct role in the molecular pathology B-CL

Standardization of molecular monitoring of CML: results and recommendations from the European treatment and outcome study

Standardized monitoring of BCR::ABL1 mRNA levels is essential for the management of chronic myeloid leukemia (CML) patients. From 2016 to 2021 the European Treatment and Outcome Study for CML (EUTOS) explored the use of secondary, lyophilized cell-based BCR::ABL1 reference panels traceable to the World Health Organization primary reference material to standardize and validate local laboratory tests. Panels were used to assign and validate conversion factors (CFs) to the International Scale and assess the ability of laboratories to assess deep molecular response (DMR). The study also explored aspects of internal quality control. The percentage of EUTOS reference laboratories (n = 50) with CFs validated as optimal or satisfactory increased from 67.5% to 97.6% and 36.4% to 91.7% for ABL1 and GUSB, respectively, during the study period and 98% of laboratories were able to detect MR4.5 in most samples. Laboratories with unvalidated CFs had a higher coefficient of variation for BCR::ABL1(IS) and some laboratories had a limit of blank greater than zero which could affect the accurate reporting of DMR. Our study indicates that secondary reference panels can be used effectively to obtain and validate CFs in a manner equivalent to sample exchange and can also be used to monitor additional aspects of quality assurance.</p

Response to tyrosine kinase hnhibitors in myeloproliferative neoplasia with 8p11 translocation and CEP110-FGFR1 rearrangement

This brief communication reports on a patient with an exceedingly rare "8p11 (eight-p-eleven) myeloproliferative syndrome" (EMS) with CEP110-FGFR1 rearrangement who responded to treatment with the multi-tyrosine kinase inhibitor (TKI) dasatinib. Dasatinib improved quality of life substantially by increasing blood counts and reducing the need for transfusions. This report demonstrates that the second-generation TKI may provide a therapeutic option for elderly and frail EMS patients who cannot be offered aggressive therapy, including allogeneic hematopoietic cell transplantatio

Traitement de la leucémie myéloïde chronique 2007: Recommandations du groupe suisse de travail de la LMC [Treatment of CML in 2007 : Recommendations of a Swiss expert panel]

- Le rapport évoque des recommandations relatives au diagnostic, au traitement initial et au suivi des patients, chez lesquels une leucémie myéloïde chronique vient d'être diagnostiquée. - Etablir un diagnostic initial complet, ainsi que procéder à une analyse de la moelle osseuse et une évaluation du risque d'une transplantation allogénique de cellules souches hématopoïétiques (allogreffe) fait partie d'un traitement adéquat. - Les patients devraient, dans la mesure du possible, être traités dans le cadre d'une étude multicentrique prospective. - Hors du cadre d'une étude clinique, le traitement de première intention des patients en phase chronique est une dose quotidienne de 400 mg d'imatinib. - Les résultats du traitement doivent être contrôlés à des moments bien précis, soit à 3, 6, 12 et 18 mois après l'établissement du diagnostic et l'instauration du traitement, et si nécessaire, la stratégie du traitement doit être modifiée. - En cas de réponse insuffisante à l'imatinib, on pourra recourir aux inhibiteurs de l'activité tyrosine kinase de deuxième génération, le dasatinib ou le nilotinib, ou à la transplantation allogénique de cellules souches hématopoïétiques. Le choix du traitement dépend du profil de risque de chaque individu